Direct One‐Pot Reductive N‐Alkylation of Nitroarenes by using Alcohols with Supported Gold Catalysts

Abstract

The formation of C N bonds is one of the most important transformations in chemistry because nitrogen-containing compounds, particularly amines and their derivatives, are versatile building blocks for various organic molecules and essential precursors to a variety of biologically active compounds. Although several methods are known for the synthesis of C N bonds, preparation under mild and wastefree conditions using simple, inexpensive, and readily available feedstock is still a challenging goal. The transitionmetal-catalyzed coupling of amines with alcohols by using a hydrogen-borrowing strategy (also known as a hydrogenautotransfer process) has proven to be an atom-economical and environmentally attractive method for the construction of C N bonds, especially for secondary amine preparation. Although many efficient catalysts for such transformations have been reported, 4] the development of easily recoverable and recyclable heterogeneous catalysts that can solve the problem of the homogeneous systems has attracted special attention. To the best of our knowledge, few heterogeneous catalyst systems have been reported that enable efficient and selective N-alkylation of amines with alcohols under simple, mild, and environmentally benign conditions. Nitroarenes are cheap and readily available organic compounds and the reduction of nitro compounds is a key step in the preparation of many pharmaceutical agents and fine chemicals. Despite numerous established procedures for the reduction of nitro compounds, the development of catalytic methodologies that afford high chemoand regioselectivity under mild reaction conditions is still a challenging problem. As for the synthesis of secondary amines, the direct use of commercially available and inexpensive nitroarenes and alcohols as starting materials is highly attractive, especially when a single catalyst system could be employed. In this valuable one-pot multistep transformation, the alcohol may conceivably serve two possible functions: as the hydrogen source for nitro reduction and as the alkylating reagent based on the catalytic hydrogen transfer. Although excess alcohol is required to ensure the completion of the reaction (see the Supporting Information for possible reaction stoichiometries), the operational simplicity of such transformations may have practical advantages for a concise synthesis of N-substituted amines in a more straightforward manner. Compared to the great progress being made in the amination of amines with alcohols, there are scarcely available reports dealing with the direct amination of nitroarenes with alcohols. To date, only three Ru-based homogeneous systems have been reported. However, these homogeneous catalysts are problematic in terms of the recovery/ recycling of the catalyst and the necessity of special handling of metal complexes. From a sustainable point of view, a more efficient reaction with a ligand-free heterogeneous catalyst is highly desired. Over the last five years, we have been interested in the unique catalytic properties of supported gold nanoparticles (NPs) and involved in their application to sustainable organic synthesis. Recently, we have shown that very small Au NPs (approx. 1.8 nm) deposited on TiO2 (Au/TiO2-VS; VS=very small) acts as an efficient heterogeneous catalyst for the clean and atom-efficient mono-N-alkylation of a range of amines with alcohols in excellent yields under hydrogen-borrowing conditions. In view of the prominent efficiency of the gold system for the amination of amines with alcohols, we envisioned that the Au-mediated hydrogen-borrowing strategy could afford a green and efficient protocol for the direct amination of nitroarenes with alcohols under mild conditions. Herein, we report for the first time that the simple Au/TiO2-VS system can catalyze the selective secondary or tertiary amine formation from the direct condensation of nitroarenes and alcohols. Notably, the reaction can proceed effectively under ligandand basefree conditions without any external hydrogen resources. To the best of our knowledge, this study also forms the first report of a one-pot selective preparation of imines from nitroarenes and alcohols by using a heterogeneous gold-mediated “catalytic hydrogen-transfer” procedure. Based on our previous results in heterogeneous Au-catalyzed amine/alcohol coupling chemistry, the optimization study was initiated with the direct amination of nitrobenzene (1a) with eight equivalents of benzyl alcohol (2a) in the presence of Au/TiO2-VS (0.5 mol% of Au, see the Sup[a] C.-H. Tang, L. He, Dr. Y.-M. Liu, Prof. Dr. Y. Cao, Prof. Dr. H.-Y. He, Prof. K.-N. Fan Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Department of Chemistry, Fudan University Shanghai 200433 (P.R. China) Fax: (+86)21-65643774 E-mail : yongcao@fudan.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201100393.